Amber Mills and colleagues new paper Maternal use of electronic cigarettes and impact on offspring: a double-hit model is a follow-up study to their earlier work showing that mother (rat) exposure to e-cigarette aerosol during pregnancy harmed offspring. The new study shows that the adverse effects of in utero (i.e., to the developing fetuses in the uterus during pregnancy) persist into adolescence and adulthood, including increased sensitivity to damage done by e-cig aerosol exposure.
Like the earlier study, they exposed pregnant rats to e-cigarette aerosol, then examined the effects on their offspring. The new study allowed the newborn pups to grow into adolescence and adulthood, at which time they were exposed to e-cig aerosol again. Mills and colleges found that the children of rats exposed while pregnant not only had greater vascular dysfunction, increased oxidative stress, and more evidence of anxiety behavior (reflecting nervous system dysfunction) compared with rats whose mothers were not exposed to e-cig aerosol while pregnant but had larger responses to e-cig exposure as adolescents and adults.
Specifically, they found that a second insult from direct vaping during adolescence or adulthood in offspring with prior in utero exposure induces greater vascular dysfunction, increased oxidative stress, and shows evidence of neuronal dysfunction compared with either direct- or maternal-only exposure. The authors conclude, “offspring with in utero exposure are predisposed to worse vascular and metabolic outcomes if they experience direct exposure to Ecig in their postnatal life.”
The levels of e-cig exposure were not large, just 60 puffs/day (1 puff every 3 min over 90 min), 5 days/wk for 3 weeks. In addition, the e-cigarette aerosol was just propylene glycol and vegetable glycerin (PG/VG) — the main component of e-liquid that e-cig advocates (and the FDA) assume is safe without any nicotine, providing more evidence that PG/VG is itself dangerous.
This study adds to the evidence that it is important to look beyond the combustion products cigarettes produce and to consider more subtle adverse effects than just birth weight when assessing the adverse effects of e-cigs and developing fetuses.
This study also adds to the evidence that the FDA was on the right track in 2019 when it proposed updating its list of Harmful and Potentially Harmful Compounds (HPHC) in tobacco products to add PG/VG (and other things). FDA never issued a final updated list; it needs to finish the job now.
Here is the abstract:
Endothelial dysfunction is a predictor for cardiovascular disease. Pre-clinical data suggest longstanding cardiovascular and cerebrovascular dysfunction occurs in offspring with perinatal electronic cigarette (Ecig) exposure. Further, direct use of Ecigs increases reactive oxygen species and impairs cerebrovascular function, but the combined effect of direct use in offspring with a history of perinatal exposure (i.e. double-hit condition) is not known. We tested the hypothesis that offspring with double-hit Ecig exposure will lead to greater cerebrovascular and neurocognitive dysfunction compared to in utero exposure only. Male and female offspring were obtained from time-mated Sprague Dawley female rats exposed to air (n=5 dams) or Ecig exposed (n=5 dams) and studied at either 3- or 6-months after birth. Ecig exposure for double-hit offspring began at 1-month before the timepoints and lasted 4-weeks (5-days/week with 90-min exposure/day). We found double-hit offspring (Ecig:Ecig=exposure dam:offspring) sustained further blunted MCA reactivity, increased severity of neuronal damage, and increased interactions of astrocytes and endothelial cells compared to offspring with maternal (Ecig:Air) or direct (Air:Ecig) exposure only. Circulating extracellular vesicles (EVs) were increased, while SIRT1 was decreased, in all Ecig exposed groups compared to controls (Air:Air), with Ecig:Ecig group showing the greatest respective change for each. Electron paramagnetic resonance spectroscopy revealed oxidative stress was the highest in the plasma of Ecig:Ecig group(p<0.05) than the other groups. These data show that a double-hit exposure in adolescent or adult offspring results in a greater decline in cerebrovascular function, biomarkers of neuronal dysfunction, and increased circulation of EVs compared to a single-hit exposure.
The full citation is: Mills A, Velayutham M, Corbin D, Suter L, Robinson M, Khramtsov VV, Shouldis L, Cook M, Dakhallah D, Chantler PD, Olfert IM. Maternal Use of Electronic Cigarettes and Impact on Offspring: A Double-Hit Model. J Appl Physiol (1985). 2024 Aug 1. doi: 10.1152/japplphysiol.00345.2024. Epub ahead of print. PMID: 39088647. It is available here.
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